-
Annual Review of Biomedical Engineering Jun 2022An integrative approach based on microfluidic design and stem cell biology enables capture of the spatial-temporal environmental evolution underpinning epigenetic... (Review)
Review
An integrative approach based on microfluidic design and stem cell biology enables capture of the spatial-temporal environmental evolution underpinning epigenetic remodeling and the morphogenetic process. We examine the body of literature that encompasses microfluidic applications where human induced pluripotent stem cells are derived starting from human somatic cells and where human pluripotent stem cells are differentiated into different cell types. We focus on recent studies where the intrinsic features of microfluidics have been exploited to control the reprogramming and differentiation trajectory at the microscale, including the capability of manipulating the fluid velocity field, mass transport regime, and controllable composition within micro- to nanoliter volumes in space and time. We also discuss studies of emerging microfluidic technologies and applications. Finally, we critically discuss perspectives and challenges in the field and how these could be instrumental for bringing about significant biological advances in the field of stem cell engineering.
Topics: Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Lab-On-A-Chip Devices; Microfluidics; Pluripotent Stem Cells
PubMed: 35378044
DOI: 10.1146/annurev-bioeng-092021-042744 -
Trends in Biotechnology Mar 2023We review the emergence of the new field of organ-on-a-chip (OOAC) engineering, from the parent fields of tissue engineering and microfluidics. We place into perspective... (Review)
Review
We review the emergence of the new field of organ-on-a-chip (OOAC) engineering, from the parent fields of tissue engineering and microfluidics. We place into perspective the tools and capabilities brought into the OOAC field by early tissue engineers and microfluidics experts. Liver-on-a-chip and heart-on-a-chip are used as two case studies of systems that heavily relied on tissue engineering techniques and that were amongst the first OOAC models to be implemented, motivated by the need to better assess toxicity to human tissues in preclinical drug development. We review current challenges in OOAC that often stem from the same challenges in the parent fields, such as stable vascularization and drug absorption.
Topics: Humans; Tissue Engineering; Microtechnology; Lab-On-A-Chip Devices; Liver; Microfluidics
PubMed: 36725464
DOI: 10.1016/j.tibtech.2022.12.018 -
Nature Communications Aug 2019The versatile and tunable self-assembly properties of nucleic acids and engineered nucleic acid constructs make them invaluable in constructing microscale and nanoscale...
The versatile and tunable self-assembly properties of nucleic acids and engineered nucleic acid constructs make them invaluable in constructing microscale and nanoscale devices, structures and circuits. Increasing the complexity, functionality and ease of assembly of such constructs, as well as interfacing them to the macroscopic world requires a multifaceted and programmable fabrication approach that combines efficient and spatially resolved nucleic acid synthesis with multiple post-synthetic chemical and enzymatic modifications. Here we demonstrate a multi-level photolithographic patterning approach that starts with large-scale in situ surface synthesis of natural, modified or chimeric nucleic acid molecular structures and is followed by chemical and enzymatic nucleic acid modifications and processing. The resulting high-complexity, micrometer-resolution nucleic acid surface patterns include linear and branched structures, multi-color fluorophore labeling and programmable targeted oligonucleotide immobilization and cleavage.
Topics: Biosensing Techniques; Cross-Linking Reagents; Fluorescence; Light; Microtechnology; Nucleic Acid Conformation; Nucleic Acids; Oligonucleotides; Photochemical Processes
PubMed: 31444344
DOI: 10.1038/s41467-019-11670-3 -
Nature Reviews. Drug Discovery Aug 2012The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea... (Review)
Review
The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.
Topics: Animal Testing Alternatives; Animals; Drug Design; Drug Discovery; Humans; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Microtechnology; Models, Biological
PubMed: 22850786
DOI: 10.1038/nrd3799 -
Medical & Biological Engineering &... Oct 2010Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade.... (Review)
Review
Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade. Due to the low costs and simple procedures, these techniques have become important and popular for biological studies. In this review, we focus on the studies integrating micro/nano-fabrication work to elucidate the molecular mechanism of signaling transduction in cell biology. We first describe different micro/nano-fabrication technologies, including techniques generating three-dimensional scaffolds for tissue engineering. We then introduce the application of these technologies in manipulating the physical or chemical micro/nano-environment to regulate the cellular behavior and response, such as cell life and death, differentiation, proliferation, and cell migration. Recent advancement in integrating the micro/nano-technologies and live cell imaging are also discussed. Finally, potential schemes in cell biology involving micro/nano-fabrication technologies are proposed to provide perspectives on the future research activities.
Topics: Cell Physiological Phenomena; Humans; Microtechnology; Nanotechnology; Tissue Engineering; Tissue Scaffolds
PubMed: 20490938
DOI: 10.1007/s11517-010-0632-z -
Cells Apr 2022Compared to cell suspensions or monolayers, 3D cell aggregates provide cellular interactions organized in space and heterogeneity that better resume the real... (Review)
Review
Compared to cell suspensions or monolayers, 3D cell aggregates provide cellular interactions organized in space and heterogeneity that better resume the real organization of native tissues. They represent powerful tools to narrow down the gap between in vitro and in vivo models, thanks to their self-evolving capabilities. Recent strategies have demonstrated their potential as building blocks to generate microtissues. Developing specific methodologies capable of organizing these cell aggregates into 3D architectures and environments has become essential to convert them into functional microtissues adapted for regenerative medicine or pharmaceutical screening purposes. Although the techniques for producing individual cell aggregates have been on the market for over a decade, the methodology for engineering functional tissues starting from them is still a young and quickly evolving field of research. In this review, we first present a panorama of emerging cell aggregates microfabrication and assembly technologies. We further discuss the perspectives opened in the establishment of functional tissues with a specific focus on controlled architecture and heterogeneity to favor cell differentiation and proliferation.
Topics: Cell Cycle; Cell Differentiation; Microtechnology; Regenerative Medicine; Tissue Engineering
PubMed: 35563700
DOI: 10.3390/cells11091394 -
Chemphyschem : a European Journal of... May 2018Probe techniques for monitoring in vivo chemistry (e.g., electrochemical sensors and microdialysis sampling probes) have significantly contributed to a better... (Review)
Review
Probe techniques for monitoring in vivo chemistry (e.g., electrochemical sensors and microdialysis sampling probes) have significantly contributed to a better understanding of neurotransmission in correlation to behaviors and neurological disorders. Microfabrication allows construction of neural probes with high reproducibility, scalability, design flexibility, and multiplexed features. This technology has translated well into fabricating miniaturized neurochemical probes for electrochemical detection and sampling. Microfabricated electrochemical probes provide a better control of spatial resolution with multisite detection on a single compact platform. This development allows the observation of heterogeneity of neurochemical activity precisely within the brain region. Microfabricated sampling probes are starting to emerge that enable chemical measurements at high spatial resolution and potential for reducing tissue damage. Recent advancement in analytical methods also facilitates neurochemical monitoring at high temporal resolution. Furthermore, a positive feature of microfabricated probes is that they can be feasibly built with other sensing and stimulating platforms including optogenetics. Such integrated probes will empower researchers to precisely elucidate brain function and develop novel treatments for neurological disorders.
Topics: Animals; Brain; Brain Chemistry; Electrochemical Techniques; Humans; Microelectrodes; Microtechnology
PubMed: 29405568
DOI: 10.1002/cphc.201701180 -
Annual Review of Biomedical Engineering 2009Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of... (Review)
Review
Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of the resulting cellular responses. High-throughput adaptations of these assays, known as living-cell microarrays, which are based on microtiter plates, high-density spotting, microfabrication, and microfluidics technologies, are being developed for two general applications: (a) to screen large-scale chemical and genomic libraries and (b) to systematically investigate the local cellular microenvironment. These emerging experimental platforms offer exciting opportunities to rapidly identify genetic determinants of disease, to discover modulators of cellular function, and to probe the complex and dynamic relationships between cells and their local environment.
Topics: Animals; Cell Culture Techniques; Cellular Structures; Genomics; Green Fluorescent Proteins; Humans; Magnetics; Microfluidic Analytical Techniques; Microfluidics; Microtechnology; Oligonucleotide Array Sequence Analysis; RNA Interference; Time Factors; Transfection
PubMed: 19413510
DOI: 10.1146/annurev.bioeng.10.061807.160502 -
Philosophical Transactions of the Royal... Jul 2018Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on... (Review)
Review
Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of human tissue engineering has gained increasing importance over the last 10 years. Technologies such as protein micropatterning, microfluidics, three-dimensional scaffolds and bioprinting have revolutionized platforms as well as increased the long-term phenotypic stability of both primary cells and stem cell-derived differentiated cells. Here, we discuss advances in engineering approaches for constructing human liver and heart models with utility for drug development. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues. Overall, bioengineered liver and heart models have significantly advanced our understanding of organ function and injury, which will prove useful for mitigating the risk of drug-induced organ toxicity to human patients, reducing animal usage for preclinical drug testing, aiding in the discovery of novel therapeutics against human diseases, and ultimately for applications in regenerative medicine.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.
Topics: Drug Development; Heart; Humans; Liver; Microfluidics; Microtechnology; Regenerative Medicine; Tissue Engineering
PubMed: 29786560
DOI: 10.1098/rstb.2017.0225 -
Biomedical Microdevices Apr 2019Cells interact intimately with complex microdomains in their extracellular matrix (ECM) and maintain a delicate balance of mechanical forces through mechanosensitive... (Review)
Review
Cells interact intimately with complex microdomains in their extracellular matrix (ECM) and maintain a delicate balance of mechanical forces through mechanosensitive cellular components. Tissue injury results in acute degradation of the ECM and disruption of cell-ECM contacts, manifesting in loss of cytoskeletal tension, leading to pathological cell transformation and the onset of disease. Recently, microscale hydrogel constructs have been developed to provide cells with microdomains to form focal adhesion binding sites, which enable restoration of cytoskeletal tension. These synthetic anchors can recapitulate the complex 3D architecture of the native ECM to provide microtopographical cues. The mechanical deformation of proteins at the cell surface can activate signaling cascades to modulate downstream gene-level transcription, making this a unique materials-based approach for reprogramming cell behavior. An overview of the mechanisms underlying these mechanosensitive interactions in fibroblasts, stem and other cell types is provided to review their effects on cellular reprogramming. Recent investigations on the fabrication, functionalization and implementation of these materials and microtopographical features for drug testing and therapeutic applications are discussed.
Topics: Animals; Cellular Reprogramming Techniques; Drug Delivery Systems; Humans; Microtechnology; Phenotype; Signal Transduction
PubMed: 30955102
DOI: 10.1007/s10544-019-0394-9